The objectives of this research effort will be to acquire information on the nature of biological activity of narcotics and their antagonists in experimental animals and in man. These efforts will be pursued by utilizing labelled substrates and techniques developed in our laboratories. The information thus obtained will serve as a guide to the desired biological characteristics. At the same time we shall also proceed with the synthesis of other derivatives of the basic naloxone and naltrexone structures to obtain compounds with an improved pharmacological profile. The proposed work therefore represents a dual approach to the problem of using narcotic antagonists for the treatment of opiate addiction, and will hopefully provide a rational means for their use in therapy.